NM_018088.3:c.1224G>C

Variant names:

• chr12-8221993-C-G
• rs11044099
• NM_018088.3:c.1224G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_018088.3(FAM90A1):​c.1224G>C​(p.Leu408Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,597,348 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00028 (2 hom.)
• Consequence: FAM90A1 NM_018088.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650
• Publications: 0 publications found

Genes affected

FAM90A1 (HGNC:25526): (family with sequence similarity 90 member A1) FAM90A1 belongs to subfamily I of the primate-specific FAM90A gene family, which originated from multiple duplications and rearrangements (Bosch et al., 2007 [PubMed 17684299]).[supplied by OMIM, Oct 2009]

FAM66C (HGNC:21644): (family with sequence similarity 66 member C)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 12-8221993-C-G is Benign according to our data. Variant chr12-8221993-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2642686.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.065 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018088.3. 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
	FAM90A1	NM_018088.3	MANE Select	c.1224G>C	p.Leu408Leu	synonymous	Exon 7 of 7	NP_060558.3	Q86YD7
	FAM90A1	NM_001319982.2		c.1224G>C	p.Leu408Leu	synonymous	Exon 6 of 6	NP_001306911.1	Q86YD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM90A1	ENST00000538603.6	TSL:1 MANE Select	c.1224G>C	p.Leu408Leu	synonymous	Exon 7 of 7	ENSP00000445418.1	Q86YD7
	FAM90A1	ENST00000307435.10	TSL:2	c.1224G>C	p.Leu408Leu	synonymous	Exon 6 of 6	ENSP00000307798.6	Q86YD7
	FAM90A1	ENST00000890758.1		c.1224G>C	p.Leu408Leu	synonymous	Exon 7 of 7	ENSP00000560817.1

Frequencies

GnomAD3 genomes AF: 0.000453 AC: 69 AN: 152208 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000428 AC: 101 AN: 235740 AF XY: 0.000479

Gnomad AFR exome AF: 0.000140

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.000605

Gnomad EAS exome AF: 0.00188

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000277 AC: 400 AN: 1445022 Hom.: 2 Cov.: 31 AF XY: 0.000286 AC XY: 206 AN XY: 719280

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000120 AC: 4 AN: 33398

American (AMR) AF: 0.000201 AC: 9 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26122

East Asian (EAS) AF: 0.00106 AC: 42 AN: 39674

South Asian (SAS) AF: 0.000650 AC: 56 AN: 86132

European-Finnish (FIN) AF: 0.0000757 AC: 3 AN: 39626

Middle Eastern (MID) AF: 0.000725 AC: 3 AN: 4140

European-Non Finnish (NFE) AF: 0.000216 AC: 240 AN: 1111132

Other (OTH) AF: 0.000516 AC: 31 AN: 60090

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000446 AC: 68 AN: 152326 Hom.: 1 Cov.: 34 AF XY: 0.000510 AC XY: 38 AN XY: 74492

African (AFR) AF: 0.000168 AC: 7 AN: 41574

American (AMR) AF: 0.000196 AC: 3 AN: 15310

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

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5176

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000400 Hom.: 0

Bravo AF: 0.000400

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.35
DANN	Benign	0.44
PhyloP100		0.065
Mutation Taster		=100/0	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: rs11044099; hg19: chr12-8374589;