17-28758335-C-T

Variant names:

• chr17-28758335-C-T
• rs36029715
• NM_001077498.3:c.1624G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001077498.3(FAM222B):​c.1624G>A​(p.Gly542Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,611,720 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (8 hom.)
• Consequence: FAM222B NM_001077498.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.34
• Publications: 1 publications found

Genes affected

FAM222B (HGNC:25563): (family with sequence similarity 222 member B) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020047128).
• BP6: Variant 17-28758335-C-T is Benign according to our data. Variant chr17-28758335-C-T is described in ClinVar as Benign. ClinVar VariationId is 780419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00635 (966/152210) while in subpopulation AFR AF = 0.0222 (922/41520). AF 95% confidence interval is 0.021. There are 9 homozygotes in GnomAd4. There are 444 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM222B	NM_001077498.3	MANE Select	c.1624G>A	p.Gly542Ser	missense	Exon 3 of 3	NP_001070966.1	Q8WU58
	FAM222B	NM_001288631.2		c.1630G>A	p.Gly544Ser	missense	Exon 4 of 4	NP_001275560.1
	FAM222B	NM_001288632.2		c.1624G>A	p.Gly542Ser	missense	Exon 5 of 5	NP_001275561.1	Q8WU58

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM222B	ENST00000581407.6	TSL:1 MANE Select	c.1624G>A	p.Gly542Ser	missense	Exon 3 of 3	ENSP00000462419.1	Q8WU58
	FAM222B	ENST00000582266.6	TSL:1	c.*1425G>A		3_prime_UTR	Exon 3 of 3	ENSP00000462534.1	J3KSK8
	FAM222B	ENST00000452648.8	TSL:2	c.1624G>A	p.Gly542Ser	missense	Exon 3 of 3	ENSP00000413645.3	Q8WU58

Frequencies

GnomAD3 genomes AF: 0.00633 AC: 963 AN: 152092 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00155 AC: 383 AN: 246490 AF XY: 0.00110

Gnomad AFR exome AF: 0.0218

Gnomad AMR exome AF: 0.00112

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.000837

GnomAD4 exome AF: 0.000658 AC: 960 AN: 1459510 Hom.: 8 Cov.: 30 AF XY: 0.000555 AC XY: 403 AN XY: 726040

African (AFR) AF: 0.0238 AC: 794 AN: 33386

American (AMR) AF: 0.00118 AC: 52 AN: 44182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25908

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.000696 AC: 4 AN: 5748

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1110982

Other (OTH) AF: 0.00143 AC: 86 AN: 60250

GnomAD4 genome AF: 0.00635 AC: 966 AN: 152210 Hom.: 9 Cov.: 32 AF XY: 0.00597 AC XY: 444 AN XY: 74410

African (AFR) AF: 0.0222 AC: 922 AN: 41520

American (AMR) AF: 0.00190 AC: 29 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68012

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00259 Hom.: 4

Bravo AF: 0.00707

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0153 AC: 60

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00175 AC: 211

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.021
Sift	Benign	0.53	T
Sift4G	Benign	0.50	T
Polyphen		0.021	B
Vest4		0.098
MVP		0.043
MPC		0.11
ClinPred		0.0086	T
GERP RS		2.7
Varity_R		0.060
gMVP		0.20
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs36029715; hg19: chr17-27085353; COSMIC: COSV99049870; COSMIC: COSV99049870;