21-41323076-G-T

Variant names:

• chr21-41323076-G-T
• rs144493544
• NM_058186.4:c.163+10G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_058186.4(FAM3B):​c.163+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM3B NM_058186.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581
• Publications: 0 publications found

Genes affected

FAM3B (HGNC:1253): (FAM3 metabolism regulating signaling molecule B) Involved in insulin secretion. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058186.4. 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
	FAM3B	NM_058186.4	MANE Select	c.163+10G>T		intron	N/A	NP_478066.3
	FAM3B	NM_206964.2		c.19+6178G>T		intron	N/A	NP_996847.1	P58499-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM3B	ENST00000357985.7	TSL:1 MANE Select	c.163+10G>T		intron	N/A	ENSP00000350673.2	P58499-1
	FAM3B	ENST00000398652.7	TSL:1	c.280+10G>T		intron	N/A	ENSP00000381646.3	P58499-2
	FAM3B	ENST00000398647.7	TSL:1	c.19+6178G>T		intron	N/A	ENSP00000381642.3	P58499-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449484 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 721372

African (AFR) AF: 0.00 AC: 0 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5190

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111642

Other (OTH) AF: 0.00 AC: 0 AN: 60254

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.011
DANN	Benign	0.50
PhyloP100		-0.58
PromoterAI		0.011	Neutral

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: rs144493544; hg19: chr21-42695003;