NM_173550.4:c.221T>C

Variant names:

• chr9-15578892-T-C
• rs115940611
• NM_173550.4:c.221T>C

Variant summary

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

The NM_173550.4(CCDC171):​c.221T>C​(p.Val74Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00178 in 1,613,702 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (25 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (37 hom.)
• Consequence: CCDC171 NM_173550.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.73
• Publications: 4 publications found

Genes affected

CCDC171 (HGNC:29828): (coiled-coil domain containing 171)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.008176684).
• BP6: Variant 9-15578892-T-C is Benign according to our data. Variant chr9-15578892-T-C is described in ClinVar as Benign. ClinVar VariationId is 790064.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 = 0.00945 (1438/152128) while in subpopulation AFR AF = 0.0331 (1373/41488). AF 95% confidence interval is 0.0316. There are 25 homozygotes in GnomAd4. There are 685 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173550.4. 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
	CCDC171	NM_173550.4	MANE Select	c.221T>C	p.Val74Ala	missense	Exon 4 of 26	NP_775821.2
	CCDC171	NM_001348002.2		c.-221T>C		5_prime_UTR_premature_start_codon_gain	Exon 4 of 27	NP_001334931.1
	CCDC171	NM_001355547.1		c.221T>C	p.Val74Ala	missense	Exon 3 of 25	NP_001342476.1	Q6TFL3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC171	ENST00000380701.8	TSL:1 MANE Select	c.221T>C	p.Val74Ala	missense	Exon 4 of 26	ENSP00000370077.3	Q6TFL3-1
	CCDC171	ENST00000905141.1		c.221T>C	p.Val74Ala	missense	Exon 4 of 26	ENSP00000575200.1
	CCDC171	ENST00000971281.1		c.221T>C	p.Val74Ala	missense	Exon 4 of 26	ENSP00000641340.1

Frequencies

GnomAD3 genomes AF: 0.00944 AC: 1435 AN: 152010 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00221 AC: 556 AN: 251044 AF XY: 0.00156

Gnomad AFR exome AF: 0.0318

Gnomad AMR exome AF: 0.000754

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000979 AC: 1431 AN: 1461574 Hom.: 37 Cov.: 30 AF XY: 0.000827 AC XY: 601 AN XY: 727108

African (AFR) AF: 0.0355 AC: 1188 AN: 33456

American (AMR) AF: 0.00112 AC: 50 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5760

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111858

Other (OTH) AF: 0.00179 AC: 108 AN: 60386

GnomAD4 genome AF: 0.00945 AC: 1438 AN: 152128 Hom.: 25 Cov.: 32 AF XY: 0.00921 AC XY: 685 AN XY: 74380

African (AFR) AF: 0.0331 AC: 1373 AN: 41488

American (AMR) AF: 0.00301 AC: 46 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67994

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00356 Hom.: 17

Bravo AF: 0.0105

ESP6500AA AF: 0.0318 AC: 140

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00286 AC: 347

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

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	Uncertain	0.40
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0082	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.7
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.29	T
Polyphen		1.0	D
Vest4		0.60
MVP		0.15
ClinPred		0.025	T
GERP RS		5.0
Varity_R		0.24
gMVP		0.068
Mutation Taster		=96/4	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: rs115940611; hg19: chr9-15578890;